title: Pre-treatment with calcium prevents endothelial cell activation induced by multiple activators, necrotic trophoblastic debris or IL-6 or preeclamptic sera: possible relevance to the pathogenesis of preeclampsia.
abstract: BACKGROUND
  A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to "toxins" from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and others include inflammatory cytokines. Calcium supplementation appears to protect "at-risk" women from developing preeclampsia by an unknown mechanism. In this study we investigate whether the addition of high levels of calcium to endothelial cells prior to their exposure to the preeclampsia-associated activators could reduce the endothelial cell activation.
  
  
  METHODS
  NTD was harvested from 1st trimester placental explants. Endothelial cells were treated with varied concentrations of calcium prior to exposure to NTD, IL-6 or preeclamptic sera or low levels of calcium. Activation was monitored by quantifying endothelial cell-surface ICAM-1 by ELISA or U937 adhesion to endothelial cells. The activity of endothelial cell nitric oxide synthetase was blocked with L-NAME.
  
  
  RESULTS
  Pre-treatment with increasing concentrations of calcium inhibited the activation of endothelial cells in response to NTD or IL-6 or preeclamptic sera. Inhibiting nitric oxide synthetase, using L-NAME, reduced the ability of high calcium levels to protect endothelial cell activation. Pre-treatment with calcium did not prevent endothelial cell activation induced by the reduction of the levels of calcium but additional calcium treatment did prevent endothelial cell activation induced by low calcium.
  
  
  CONCLUSIONS
  Our results demonstrate calcium supplementation may prevent the activation of the endothelium in response to activators. These results may partially explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in vitro mechanistic support for the use of calcium supplementation in at-risk women.
authors.affiliation: Department of Obstetrics & Gynaecology, The University of Auckland, New Zealand; The Hospital of Obstetrics & Gynaecology, Fudan University, China; Wuxi Maternity and Child Health Hospital, Nanjing Medical University, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Tong
authors.forename: M
authors.initials: M
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Snowise
authors.forename: P
authors.initials: P
authors.lastname: Stone
authors.forename: L W
authors.initials: LW
authors.lastname: Chamley
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002136:Calcium, Dietary / Q000627:therapeutic use; D002450:Cell Communication; D002460:Cell Line; D002474:Cell-Free System; D019587:Dietary Supplements; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D009336:Necrosis; D009994:Osmolar Concentration; D010920:Placenta / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D021041:Placental Circulation; D011225:Pre-Eclampsia / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D002136:Calcium, Dietary; C508600:IL6 protein, human; D015850:Interleukin-6; D011994:Recombinant Proteins; D002118:Calcium
keywords: Calcium supplementation; Endothelium; Nitric oxide; Preeclampsia; Trophoblastic debris